The overall objective of the proposal investigation is to determine the efficacy of various classes of pharmacological anti-inflammatory agents in limiting the formation of edema in burn wounds. A dual experimental modality will be followed in which methods for the treatment of burns will be evaluated in vivo in both microscopic and complete organism systems. Several groups of drugs will be tested which have specific antagonistic activity on endogenous inflammatory mediators including histamine, serotonin, the kinins, and the prostaglandins. A highly effective experimental procedure has been developed by the project investigators to study burn injury in the microcirculation of the golden hamster cheek pouch. This mesentery tissue will be prepared for direct, continuous viewing during the entire injury process on a specially modified light microscope. Standardized thermal injuries will be effected either by a novel heating and/or cooling stage coupled to a programmable temperature control system or by a laser focused through the microscope optics. The temperature time history will be measured by a 20mm microthermocouple, manufactured in our laboratory, in direct contact with the tissue specimen. Edema will be visualized by the extravasation of fluorescent tagged dextran or albumin. A sequential film record will be made of the diffusion of dye through the interstitial space. Subsequently, selected photomicrographs will be digitized with 8 bits of gray level information and analyzed on a digital computer using software developed in our laboratory. The computer analysis will determine the rate and extent of leakage from the vascular system. Burn therapies which exhibit a significant advantage in the microcirculation studies will be investigated further in a whole animal burn model. Standard thermal lesions will be created on the backs of rats by immersion in hot water. The size and rate of healing of the resulting would will be determined over a 4 week postburn period by automatic computer analysis of sequential calibrated photographs of residual wound area.